Recruiting
Phase 2

Pembrolizumab, Investigational Agents

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06788912

Conditions

Lung Neoplasm Malignant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab (neoadjuvant)

Cisplatin

Gemcitabine

Pemetrexed

Sacituzumab tirumotecan

Study Details

Brief summary:

The main goals are after treatment given before surgery, to measure the number of people who have no signs of cancer cells in tumors and lymph nodes removed during surgery; and to learn about whether the cancer gets smaller or goes away by measuring the number of people with a certain number of living cancer cells in the tumor removed during surgery.

Conditions

Lung Neoplasm Malignant

Study ID

NCT06788912

Start date

Mar 20, 2025

Status verified date

Aug, 2026

Completion date

Feb 6, 2032

Anticipated

Primary completion date

Feb 6, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

  • Has previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC)
  • Able to undergo protocol therapy, including necessary surgery
  • Confirmation that epidermal growth factor receptor (EGFR) -directed therapy is not indicated as primary therapy
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 10 days before initiation of study intervention.
  • Is able to provide archival or newly obtained core/excisional biopsy of the primary lung tumor or lymph node metastasis.

Exclusion Criteria:

  • Has one of the following tumor locations/types: NSCLC involving the superior sulcus, large-cell neuro-endocrine cancer, mixed tumors containing small cell and non-small cell elements, or sarcomatoid tumor.
  • Has Grade ≥2 peripheral neuropathy.
  • Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
  • Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
  • Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids.
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
  • Known additional malignancy that is progressing or has required active treatment within the past 5 years.
  • Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid) is allowed.
  • History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Active infection requiring systemic therapy.
  • Hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C virus (defined as detectable hepatitis C virus (HCV) ribonucleic acid (RNA) \[qualitative\]) infection.
  • Known history of human immunodeficiency virus (HIV) infection.
  • History of allogeneic tissue/solid organ transplant.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Pembrolizumab + Platinum

Neoadjuvant: Prior to surgery pembrolizumab 200 mg every three weeks (Q3W) for 4 cycles (each cycle is 21 days); Cisplatin 75 mg/m\^2 Q3W with gemcitabine 1000 mg/m\^2 on Day 1 and Day 8 Q3W (squamous tumors), pemetrexed 500 mg/m\^2 Q3W (nonsquamous tumors), or paclitaxel 175 mg/m\^2 or 200 mg/m\^2 q3w (any histology) OR Carboplatin AUC 5 mg/mL• min or AUC 6 mg/mL• min with paclitaxel 175 mg/m\^2 or 200 mg/m\^2 Q3W (any histology), pemetrexed 500 mg/m\^2 Q3W (nonsquamous tumors), or gemcitabine 1000 mg/m\^2 on Day 1 and Day 8 Q3W (squamous tumors); followed by surgery.

Adjuvant: After surgery pembrolizumab 200 mg Q3W for 13 cycles (each cycle is 21 days).

experimental: Pembrolizumab + Sacituzumab tirumotecan

Neoadjuvant: Prior to surgery pembrolizumab 200 mg Q3W for 4 cycles (each cycle is 21 days); sacituzumab tirumotecan 4 mg/kg Q2W for 6 cycles (each cycle is 14 days), followed by surgery.

Adjuvant: After surgery pembrolizumab 200 mg Q3W for 13 cycles (each cycle is 21 days). Optional adjuvant platinum-based doublet chemotherapy up to 4 cycles may be given at the investigator's discretion.

Interventions

Pembrolizumab (neoadjuvant)

Before surgery neoadjuvant Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 21-day cycle for 4 cycles

Cisplatin

Cisplatin 75 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles

Gemcitabine

In squamous tumors Gemcitabine 1000 mg/m\^2 by IV infusion on day 1 and day 8 of each 21-day cycle for 4 cycles.

Pemetrexed

In nonsquamous tumors Pemetrexed 500 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles

Sacituzumab tirumotecan

Sacituzumab tirumotecan 4 mg/kg by IV infusion on day 1 of each 14-day cycle for up to 6 cycles

H1 receptor antagonist

Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label

H2 receptor antagonist

Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label

Acetaminophen (or equivalent)

Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label

Dexamethasone (or equivalent)

Administered as rescue medication 8 -10 mg before Sacituzumab tirumotecan infusion per approved product label

Carboplatin

AUC 5 mg/mL min or AUC 6 mg/mL min by IV infusion on day 1 of each 21-day cycle for 4 cycles

Pembrolizumab (adjuvant)

After surgery adjuvant Pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for 13 cycles

Paclitaxel

Paclitaxel 175 or 200 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles.

Steroid mouthwash (dexamethasone or equivalent)

Administered orally as rescue medication 2-5 mL 4 times daily

Primary outcome measure

  • Pathological Complete Response (pCR) [ Time Frame: Up to approximately 20 weeks ]
  • Percent Residual Viable Tumor (%RVT) [ Time Frame: Up to approximately 20 weeks ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

Southern Cancer Center (SCC) ( Site 8004)

Recruiting

Daphne, Alabama, United States, 36526

Contacts

Study Coordinator

251-607-5281

Sansum Clinic (Ridley Tree) ( Site 8012)

Recruiting

Santa Barbara, California, United States, 93105

Contacts

Study Coordinator

805-879-0643

Rocky Mountain Cancer Centers (RMCC) ( Site 8011)

Recruiting

Lone Tree, Colorado, United States, 80124

Contacts

Study Coordinator

303-285-5051

Greenebaum Comprehensive Cancer Center ( Site 0402)

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Study Coordinator

410-328-2288

MedStar Franklin Square Medical Center ( Site 0033)

Recruiting

Baltimore, Maryland, United States, 21237

Contacts

Study Coordinator

443-777-7147

Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute) (WVCI) ( Site 8006)

Recruiting

Eugene, Oregon, United States, 97401

Contacts

Study Coordinator

541-683-5001

Texas Oncology - Central/South Texas ( Site 8009)

Recruiting

Austin, Texas, United States, 78705

Contacts

Study Coordinator

254-399-0741

Texas Oncology - Northeast Texas ( Site 8005)

Recruiting

Tyler, Texas, United States, 75702

Contacts

Study Coordinator

903-579-9800

Virginia Cancer Specialists (VCS) ( Site 8002)

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Study Coordinator

215-706-2034

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 1, 2026

Last verified

Aug, 2026

Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
  • Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-01.